4-99338684-T-C

Variant names:

• chr4-99338684-T-C
• rs1662060
• NM_000669.5:c.1103+893A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000669.5(ADH1C):​c.1103+893A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 147,038 control chromosomes in the GnomAD database, including 8,470 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (8470 hom., cov: 23)
• Consequence: ADH1C NM_000669.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510
• Publications: 7 publications found

Genes affected

ADH1C (HGNC:251): (alcohol dehydrogenase 1C (class I), gamma polypeptide) This gene encodes class I alcohol dehydrogenase, gamma subunit, which is a member of the alcohol dehydrogenase family. Members of this enzyme family metabolize a wide variety of substrates, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. Class I alcohol dehydrogenase, consisting of several homo- and heterodimers of alpha, beta, and gamma subunits, exhibits high activity for ethanol oxidation to acetaldehyde, thus playing a major role in ethanol catabolism. Three genes encoding alpha, beta and gamma subunits are tandemly organized in a genomic segment as a gene cluster. An association between ADH1C polymorphism and alcohol dependence has not been established. [provided by RefSeq, Sep 2019]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000669.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH1C	NM_000669.5	MANE Select	c.1103+893A>G		intron	N/A	NP_000660.1	P00326
	ADH1C	NR_133005.2		n.1130+893A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH1C	ENST00000515683.6	TSL:1 MANE Select	c.1103+893A>G		intron	N/A	ENSP00000426083.1	P00326
	ADH1C	ENST00000865215.1		c.1103+893A>G		intron	N/A	ENSP00000535274.1
	ADH1C	ENST00000865216.1		c.1103+893A>G		intron	N/A	ENSP00000535275.1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 45461 AN: 146922 Hom.: 8463 Cov.: 23

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.0808

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.270

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.309 AC: 45482 AN: 147038 Hom.: 8470 Cov.: 23 AF XY: 0.308 AC XY: 21963 AN XY: 71194

African (AFR) AF: 0.141 AC: 5632 AN: 39998

American (AMR) AF: 0.284 AC: 4045 AN: 14254

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 939 AN: 3450

East Asian (EAS) AF: 0.0804 AC: 405 AN: 5040

South Asian (SAS) AF: 0.285 AC: 1273 AN: 4472

European-Finnish (FIN) AF: 0.509 AC: 4924 AN: 9680

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27442 AN: 66938

Other (OTH) AF: 0.273 AC: 550 AN: 2014

Alfa AF: 0.298 Hom.: 2275

Bravo AF: 0.287

Asia WGS AF: 0.219 AC: 760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.3
DANN	Benign	0.66
PhyloP100		0.051

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1662060; hg19: chr4-100259841;